This K02 Independent Scientist Award application proposes structured career development activities in functional magnetic resonance imaging (fMRI) and candidate gene analyses, specifically to identify links between genes, brain activity, and environmental factors that lead to and maintain adolescent substance use. Current systems of classification for substance use disorders are based on careful clinical description, but increasingly available technologies in genetics and neuroimaging can help to validate and refine, possibly even restructure, conceptual models of core processes underlying addiction, such as "impaired control" over substance use. Career development activities will build on the applicant's expertise in the classification and course of adolescent substance use disorders, and will focus on two key addiction constructs: response inhibition and reward sensitivity. The aim of the proposed career development activities is to increase the candidate's knowledge and skills in fMRI (applied to an antisaccade task) and the analysis of selected candidate genes that will provide the foundation for effective collaboration with experts in neuroimaging and genetics in order to integrate these methods into longitudinal research. Career development activities in fMRI analysis will be applied to data from an antisaccade task in the context of reward, a sensitive measure of response inhibition, that have been collected in the R01 "Course of alcohol and drug problems in treated youth" (Course Study). Career development activities in the analysis of candidate genes will be applied to genetic data collected in the Course Study, and the Pittsburgh Adolescent Alcohol Research Center. Training in the integrated analysis of fMRI antisaccade and candidate gene data collected in the Course Study will be used to identify genetic associations with a neurocognitive phenotype that may predict treatment response. Hands-on training in fMRI and candidate gene analyses will be supplemented by tutorials with K02 consultants, directed readings, and course work. Support from this K02 award will provide the applicant with protected time to advance a program of alcohol research on genetic, neurocognitive, and environmental factors underlying onset, course, and response to treatment in adolescent substance users, which can be used to guide the development of effective treatment. PUBLIC HEALTH RELEVANCE: Few studies involving adolescents have integrated neuroimaging and genetic data to examine risk for early onset of substance use, substance use trajectories, and differential response to treatment. Integration of neuroimaging and genetic approaches in studies of adolescent substance use has substantial public health implications for identifying biomarkers that can be used to improve the timing and content of prevention and intervention efforts provided to youth.